The most extensively studied and consistently replicated aspect of the psychobiology of major affective disorders has been the hypersecretion, dexamethasone non-suppression and loss of diurnal periodicity of cortisol that occurs in a subgroup of patients with acute major depression. This state-dependent variable is believed to reflect central pathophysiologic systems and has been the basis of numerous investigations. However, despite the substantial amount of research, the mechanisms that mediate cortisol hypersecretion in depression are not known. The few studies that have attempted to investigate this have produced conflicting results and the primary locus of this abnormality (CNS, pituitary, or adrenal) remains to be firmly established. This study will intensively examine 27 subjects (9 acutely depressed patients with cortisol hypersecretion, 9 nonhypersecretors and 9 healthy volunteers) to elucidate the neuroendocrine mechanisms that mediate the hypersecretion of cortisol and dexamethasone nonsuppression. Under rigorously controlled conditions each subject will have serial blood samples collected at 10 minute intervals over a four hour period (1,500 to 1,900 hours) on consecutive days pre and post a 2,300 hr. oral administration of dexamethasone 1 mg. Blood samples will be assayed for cortisol, ACTH, B-endorphin, and B-lipotropin. This study will help elucidate the pathophysiology of cortisol hypersecretion in major depression and provide neuroendocrine markers of central nervous system dysfunction in this disease. Such information will be useful clinically and provide a sound basis for further investigation.